This invention relates to particles comprising silica-based, calcium and phosphate containing, glass compositions, and their transformation to calcium-phosphate shells in vitro.
In U.S. Pat. No. 5,204,106, issued to Schepers et al., (hereby incorporated by reference) the implantation of bioactive glass granules having the composition: 45% SiO2, 24.5% Na2O, 24.5% CaO and 6% P2O5, and a size range of 280-425 xcexcm in diameter into the jaw of beagle dogs is disclosed. With particles of this size range, internal pouches formed in each of the particles and, subsequently, osteoprogenitor cells differentiated to osteoblasts within the pouches, actively laying down bone tissue. Next, bone tissue proliferated from the excavations, surrounded the particles and connected with bone tissue being formed around neighboring particles. Bone tissue was formed within the particle, without being bridged to the lingual or buccal bone plates. At 3 months, bone had grown throughout the surgical defects treated with glass granules. A similar phenomenon was not observed with particles of a larger size range, i.e., 480-800 micrometers, or a smaller size range, i.e., 210-300 micrometers.
Glass granules of narrow size range (300-360 xcexcm) were used in a clinical trial in humans. Schepers et al., xe2x80x9cBioactive Glass Particles of Narrow Size Range: A New Material for the Repair of Bone Defects,xe2x80x9d Implant Dentistry, 2(3):151-156, 1993, incorporated herein by reference. In this clinical study, 87 patients and 106 maxillo facial defects were treated. At 3 months, the application sites had fully solidified. At six months, no radiological difference between the defect sites and the surrounding bone could be discerned.
It was subsequently discovered that particles in the size range 200-300 micrometers effected the same results if implanted into sites exhibiting a reduced metabolic state, particularly as compared to the maxillo-facial sites. Such sites are found, for example, in the appendicular skeleton, and in certain disease states. U.S. application Ser. No. 08/268,510, hereby incorporated by reference.
The in vivo event which initiates the reactions leading to the formation of bone throughout the defects is an excavation of the particles. The excavation is the result of physico-chemical reactions taking place in the glass, as well as a cell mediated resorption of the internal reaction layer. Bioactive glass reacts at its surface with the formation of two reaction layers: a silica gel below the surface and a calcium phosphate rich layer at the surface. In vivo, pouches of biologically formed calcium phosphate are formed. It is within these pouches that osteoprogenitor cells, which freely float around, undergo differentiation to cells expressing the osteoblastic phenotype. This differentiation does not occur outside these biologically formed calcium phosphate pouches.
Even so, it takes approximately one month for the particles to excavate in vivo. A means for further expediting the healing process would be advantageous.
The present invention can further expedite the healing process through the excavation of silica-based glass particles in vitro. According to the present invention, silica-based, Ca,P-containing glasses are transformed to hollow CaP-shells in vitro, prior to implantation. The silica-based glass granules can be melt- or sol-gel derived. The resultant hollow shells comprise an outer, nanoporous, carbonated amorphous or crystalline CaP-rich layer, with or without remaining silica.
In one aspect, the invention relates to the hollow particles which have been formed in vitro.
In another aspect, the invention relates to a method for producing the hollow calcium-phosphate particles according to the invention involving a differential immersion of the particles in solutions which provoke the dissolution of the silicon from the particles.